LncRNA SLCO4A1-AS1 promotes colorectal cancer cell proliferation by enhancing autophagy via miR-508-3p/PARD3 axis

Aging (Albany NY). 2019 Jul 16;11(14):4876-4889. doi: 10.18632/aging.102081.

Abstract

Aberrant expressions of various long non-coding RNAs (lncRNAs) have been involved in the progression and pathogenesis of various carcinomas. However, the expression and biological function of SLCO4A1-AS1 in colorectal cancer (CRC) remain poorly understood. Gain- and loss-of-function assays were applied to determine the roles of SLCO4A1-AS1 in autophagy and CRC progression. qRT-PCR and in situ hybridization (ISH) results showed that SLCO4A1-AS1 was positively associated with PARD3 expression in CRC tissues. In vitro and in vivo studies revealed that SLCO4A1-AS1 knockdown repressed cytoprotective autophagy as assayed by transmission electron microscopy (TEM), and inhibited cell proliferation by directly targeting partition-defective 3 (PARD3). Mechanistically, SLCO4A1-AS1 acted as a sponge of miR-508-3p, leading to upregulation of PARD3 and promotion of CRC cell proliferation. The current study demonstrates that the SLCO4A1-AS1/miR-508-3p/PARD3/autophagy pathway play a critical role in CRC cell proliferation, and might provide novel targets for developing therapeutic strategies for CRC.

Keywords: PARD3; SLCO4A1-AS1; autophagy; colorectal cancer (CRC); miR-508-3p.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Aged
  • Aged, 80 and over
  • Autophagy / genetics
  • Cell Cycle Proteins / genetics*
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Organic Anion Transporters / genetics*
  • RNA, Long Noncoding / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • MIRN508 microRNA, human
  • MicroRNAs
  • Organic Anion Transporters
  • PARD3 protein, human
  • RNA, Long Noncoding
  • SLCO4A1 protein, human